More than 50% of corneal transplants, the most common form of solid organ transplantation, are performed to restore vision lost secondary to corneal endothelial failure. More than 25% of those transplants will eventually fail and endothelial cell rejection leading to failure is the single most important cause. The key to protec the endothelium is the early and accurate diagnosis of cell injury to promptly initiate treatment before irreversible damage occurs. Current diagnostic techniques fall short in protecting endothelial cells. Our pilot studies, aimed at addressing this critical need, revealed great potential of using in vivo corneal endothelium/Descemet's membrane (En/DM) characteristics, disclosed using high definition optical coherence tomography (HDOCT), in diagnosing corneal graft rejection. Yet, they also highlighted technology limitations hindering establishing this nove technique. This proposed research activity will focus on advancing HDOCT technology to better describe corneal grafts En/DM and validating, in the setting of a clinical study, the utility of th developed technology to early and accurately diagnose graft rejection. This project is led by Mohamed Abou Shousha, M.D., FRCS, Ph.D., of the Bascom Palmer Eye Institute (BPEI). He is a highly trained cornea specialist with broad experience in corneal imaging and patient oriented research. His career goals include developing the knowledge and skills to become an independent clinician-scientist while establishing diagnostic techniques to better diagnose corneal endothelial injury to decrease risk of endothelial failure and test his techniques in multi center clinical trials. The three aims of this proposal reflect his goals and include: (1) development and validation of automated En/DM tomographic thickness maps, to address technology limitations that only allow manual En/DM segmentation, which is time consuming, operator dependent and ignores tomography as an important dimension of En/DM structure. (2) Development and validation of instrumentations to extend En/DM images to include the paracentral and peripheral corneal graft, to address current technology limitation, which is the inability to describe the paracentral and peripheral En/DM despite that those are where rejection typically starts. (3) Verify the prediction that wide corneal graft En/DM tomographic thickness maps can diagnose corneal graft rejection more accurately and at an earlier stage than central En/DM thickness through a proof of concept clinical study. In addition to the research activity, he has a highly structured career development plan to further his research skills and develop the solid base for a successful career as an independent clinician- scientist. He has assembled an outstanding mentorship team (Drs. Victor Perez, Fabrice Manns, and Sonia Yoo) with extensive experience in basic, translational and patient oriented research focused on corneal grafts rejection and biomedical corneal imaging technology. He has also developed a strong scientific advisory committee and partnerships with collaborators at the BPEI's McKnight Vision Research Center and Ophthalmic Biophysics Center to strengthen his proposal and the likelihood of both short-term and long-term success.